Protective effects of a G. lucidum proteoglycan on INS-1 cells against IAPP-induced apoptosis via attenuating endoplasmic reticulum stress and modulating CHOP/JNK pathways

Fudan-Yueyang-G. lucidum (FYGL) is a water-soluble macromolecular proteoglycan extracted from Ganoderma lucidum which has been used for health promotion for a long time in China. The aim of this study was to investigate the protective effects of FYGL on INS-1 rat insulinoma beta cells against IAPP-induced cell apoptosis, as well as the underlying mechanisms. The results showed that apoptotic cells were significantly increased when incubated with islet amyloid polypeptide (IAPP). However, cytotoxicity of IAPP was significantly attenuated by co-incubation of the cells with FYGL. The results of RT-PCR showed that mRNA expression of caspase-3, caspase-12 and C/EBP homologous protein (CHOP) in IAPP-treated cells were inhibited by FYGL. Moreover, FYGL significantly prevented the IAPP-induced abnormal expression of inositol-requiring protein-1α (IRE1α), protein kinase RNA (PKR)-like ER kinase (PERK), activating transcription factor 6 (ATF6), as well as suppressed the activation of CHOP and c-Jun N-terminal kinase (JNK). Taken together, our results suggest that FYGL protects INS-1 pancreatic beta cells against IAPP-induced apoptosis through attenuating endoplasmic reticulum stress (ERS) and modulating CHOP/JNK pathways.